全文获取类型
收费全文 | 1784篇 |
免费 | 171篇 |
出版年
2023年 | 10篇 |
2022年 | 18篇 |
2021年 | 39篇 |
2020年 | 12篇 |
2019年 | 20篇 |
2018年 | 40篇 |
2017年 | 24篇 |
2016年 | 56篇 |
2015年 | 89篇 |
2014年 | 94篇 |
2013年 | 117篇 |
2012年 | 176篇 |
2011年 | 149篇 |
2010年 | 108篇 |
2009年 | 101篇 |
2008年 | 136篇 |
2007年 | 108篇 |
2006年 | 88篇 |
2005年 | 104篇 |
2004年 | 101篇 |
2003年 | 103篇 |
2002年 | 109篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 16篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 2篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1972年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有1955条查询结果,搜索用时 15 毫秒
31.
Pascal I. Hablützel Filip A. M. Volckaert Bart Hellemans Joost A. M. Raeymaekers 《Immunogenetics》2013,65(11):795-809
Cichlid fishes are emblematic models for the study of adaptive radiation, driven by natural and sexual selection. Parasite mediated selection is an important component in these processes, and the evolution of their immune system therefore merits special attention. In this study, light is shed on the phylogeny of the b family of cichlid major histocompatibility complex (MHC) class IIB genes. Full-length coding sequences were used to reconstruct phylogenies using criteria of maximum parsimony, maximum likelihood and Bayesian inference. All analyses suggest monophyly of the b family of cichlid MHC class IIB genes, although sequences of the cichlid sister taxa are currently not available. Two evolutionary lineages of these genes, respectively encompassing the recently defined genomic regions DBB-DEB-DFB and DCB-DDB, show highly contrasting levels of differentiation. To explore putative causes for these differences, exon 2 sequences were screened for variation in recombination rate and strength of selection. The more diversified lineage of cichlid MHC class IIB b genes was found to have higher levels of both recombination and selection. This is consistent with the observation in other taxa that recombination facilitates the horizontal spread of positively selected sites across MHC loci and hence contributes to fast sequence evolution. In contrast, the lineage that showed low diversification might either be under stabilizing selection or is evolutionary constrained by its low recombination rate. We speculate whether this lineage might include MHC genes with non-classical functions. 相似文献
32.
Stephane Savanah 《Biology & philosophy》2013,28(4):657-673
The view that mirror self-recognition (MSR) is a definitive demonstration of self-awareness is far from universally accepted, and those who do support the view need a more robust argument than the mere assumption that self-recognition implies a self-concept (e.g. Gallup in Socioecology and Psychology of Primates, Mouton, Hague, 1975; Gallup and Suarez in Psychological Perspectives on the Self, vol 3, Erlbaum, Hillsdale, 1986). In this paper I offer a new argument in favour of the view that MSR shows self-awareness by examining the nature of the mirror image itself. I argue, using the results of ‘symbol-mindedness’ experiments by Deloache (Trends Cogn Sci 8(2):66–70, 2004), that where self-recognition exists, the mirror image must be functioning as a symbol from the perspective of the subject and the subject must therefore be ‘symbol-minded’ and hence concept possessing. Further to this, according to the Concept Possession Hypothesis of Self-Consciousness (Savanah in Conscious Cogn 2011), concept possession alone is sufficient to demonstrate the existence of self-awareness. Thus MSR as a demonstration of symbol-mindedness implies the existence of self-awareness. I begin by defending the ‘mark test’ protocol as a robust methodology for determining self-recognition. Then follows a critical examination of the extreme views both for and against the interpretation of MSR as an indication of self-awareness: although the non-mentalistic interpretation of MSR is unconvincing, the argument presented by Gallup is also inadequate. I then present the symbol-mindedness argument to fill in the gaps in the Gallup approach. 相似文献
33.
Olga Kononova Joost Snijder Melanie Brasch Jeroen Cornelissen Ruxandra?I. Dima Kenneth?A. Marx Gijs?J.L. Wuite Wouter?H. Roos Valeri Barsegov 《Biophysical journal》2013,105(8):1893-1903
Physical properties of capsids of plant and animal viruses are important factors in capsid self-assembly, survival of viruses in the extracellular environment, and their cell infectivity. Combined AFM experiments and computational modeling on subsecond timescales of the indentation nanomechanics of Cowpea Chlorotic Mottle Virus capsid show that the capsid’s physical properties are dynamic and local characteristics of the structure, which change with the depth of indentation and depend on the magnitude and geometry of mechanical input. Under large deformations, the Cowpea Chlorotic Mottle Virus capsid transitions to the collapsed state without substantial local structural alterations. The enthalpy change in this deformation state ΔHind = 11.5–12.8 MJ/mol is mostly due to large-amplitude out-of-plane excitations, which contribute to the capsid bending; the entropy change TΔSind = 5.1–5.8 MJ/mol is due to coherent in-plane rearrangements of protein chains, which mediate the capsid stiffening. Direct coupling of these modes defines the extent of (ir)reversibility of capsid indentation dynamics correlated with its (in)elastic mechanical response to the compressive force. This emerging picture illuminates how unique physico-chemical properties of protein nanoshells help define their structure and morphology, and determine their viruses’ biological function. 相似文献
34.
35.
Olga Kononova Joost Snijder Melanie Brasch Jeroen Cornelissen Ruxandra I. Dima Kenneth A. Marx Gijs J.L. Wuite Wouter H. Roos Valeri Barsegov 《Biophysical journal》2013
Physical properties of capsids of plant and animal viruses are important factors in capsid self-assembly, survival of viruses in the extracellular environment, and their cell infectivity. Combined AFM experiments and computational modeling on subsecond timescales of the indentation nanomechanics of Cowpea Chlorotic Mottle Virus capsid show that the capsid’s physical properties are dynamic and local characteristics of the structure, which change with the depth of indentation and depend on the magnitude and geometry of mechanical input. Under large deformations, the Cowpea Chlorotic Mottle Virus capsid transitions to the collapsed state without substantial local structural alterations. The enthalpy change in this deformation state ΔHind = 11.5–12.8 MJ/mol is mostly due to large-amplitude out-of-plane excitations, which contribute to the capsid bending; the entropy change TΔSind = 5.1–5.8 MJ/mol is due to coherent in-plane rearrangements of protein chains, which mediate the capsid stiffening. Direct coupling of these modes defines the extent of (ir)reversibility of capsid indentation dynamics correlated with its (in)elastic mechanical response to the compressive force. This emerging picture illuminates how unique physico-chemical properties of protein nanoshells help define their structure and morphology, and determine their viruses’ biological function. 相似文献
36.
Eukaryotic cells contain hundreds of different lipid species that are not uniformly distributed among their membranes. For example, sphingolipids and sterols form gradients along the secretory pathway with the highest levels in the plasma membrane and the lowest in the endoplasmic reticulum. Moreover, lipids in late secretory organelles display asymmetric transbilayer arrangements with the aminophospholipids concentrated in the cytoplasmic leaflet. This lipid heterogeneity can be viewed as a manifestation of the fact that cells exploit the structural diversity of lipids in organizing intracellular membrane transport. Lipid immiscibility and the generation of phase-separated lipid domains provide a molecular basis for sorting membrane proteins into specific vesicular pathways. At the same time, energy-driven aminophospholipid transporters participate in membrane deformation during vesicle biogenesis. This review will focus on how selective membrane transport relies on a dynamic interplay between membrane lipids and proteins. 相似文献
37.
Alissa Minkovsky Tahsin Stefan Barakat Nadia Sellami Mark Henry Chin Nilhan Gunhanlar Joost Gribnau Kathrin Plath 《Cell reports》2013,3(3):905-918
Download : Download video (91MB) 相似文献
38.
Devarsetty?PraveenEmail author Anushka?Patel Stephen?McMahon Dorairaj?Prabhakaran Gari?D.?Clifford Pallab?K.?Maulik Rohina?Joshi Stephen?Jan Stephane?Heritier David?Peiris 《Implementation science : IS》2013,8(1):137
Background
Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.Methods
We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.Expected outcomes
The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.Significance
The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.Trial registration
Clinical Trial Registry India CTRI/2013/06/003753.39.
Muhammad A. Javed Somayyeh Poshtiban Denis Arutyunov Stephane Evoy Christine M. Szymanski 《PloS one》2013,8(7)
Campylobacter jejuni and Campylobacter coli are the most common bacterial causes of foodborne gastroenteritis which is occasionally followed by a debilitating neuropathy known as Guillain-Barré syndrome. Rapid and specific detection of these pathogens is very important for effective control and quick treatment of infection. Most of the diagnostics available for these organisms are time consuming and require technical expertise with expensive instruments and reagents to perform. Bacteriophages bind to their host specifically through their receptor binding proteins (RBPs), which can be exploited for pathogen detection. We recently sequenced the genome of C. jejuni phage NCTC12673 and identified its putative host receptor binding protein, Gp047. In the current study, we localized the receptor binding domain to the C-terminal quarter of Gp047. CC-Gp047 could be produced recombinantly and was capable of agglutinating both C. jejuni and C. coli cells unlike the host range of the parent phage which is limited to a subset of C. jejuni isolates. The agglutination procedure could be performed within minutes on a glass slide at room temperature and was not hindered by the presence of buffers or nutrient media. This agglutination assay showed 100% specificity and the sensitivity was 95% for C. jejuni (n = 40) and 90% for C. coli (n = 19). CC-Gp047 was also expressed as a fusion with enhanced green fluorescent protein (EGFP). Chimeric EGFP_CC-Gp047 was able to specifically label C. jejuni and C. coli cells in mixed cultures allowing for the detection of these pathogens by fluorescent microscopy. This study describes a simple and rapid method for the detection of C. jejuni and C. coli using engineered phage RBPs and offers a promising new diagnostics platform for healthcare and surveillance laboratories. 相似文献
40.